Chronic Urticaria
Conditions
Brief summary
This is a Phase 2a, open-label study to assess the effects of AK002
Detailed description
This open-label study is to assess the effects of AK002, given as monthly intravenous infusions at up to 3 mg/kg. A total of 47 patients will be enrolled across 2-4 sites. All patients enrolled in the study will receive 6 monthly infusions of AK002 and will then be followed for another 8 weeks. Some patients will have the option to receive an additional 12 months of extended dosing.
Interventions
DRUGAK002
AK002 is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8, a member of the CD33-related family of sialic acid-binding, immunoglobulin-like lectins (Siglecs).
Sponsors
Allakos Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Adults (≥ 18 and ≤ 85 years old) 2. Body weight \<125 Kg 3. Informed consent signed and dated 4. Able to read, understand, and willing to sign the informed consent form and comply with study procedures 5. Diagnosis of CU for at least three months, refractory to antihistamine treatment in single or 4-fold dosage 6. Willing, committed, and able to return for all clinic visits and complete all study-related procedures, including willingness to have IV infusion of study drug administered by a qualified person 7. Females of childbearing potential must have a negative pregnancy test at Baseline. Female subjects must be willing to use highly effective contraception (Pearl- 4 Index \< 1). A woman will be considered not of childbearing potential if she is post-menopausal for greater than two years (FSH \>40mL) or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) 8. No participation in other clinical trials 4 weeks before participation in this study 9. Uncontrolled CU (UCT \<12) at the time of enrollment
Exclusion criteria
1. Acute urticaria 2. Concurrent/ongoing treatment with immunosuppressives (e.g., cyclosporine, methotrexate, dapsone, or others) within 4 weeks or 5 half-lives prior to Baseline, whichever is longer 3. Significant medical condition rendering the patient immunocompromised or not suitable for a clinical trial 4. Significant concomitant illness that would adversely affect the subject's participation or evaluation in this study 5. History of malignancies within five years prior to screening other than a successfully treated non-metastatic cutaneous, basal, or squamous cell carcinoma and/or in situ cancer 6. Presence of clinically significant laboratory abnormalities 7. Lactating women or pregnant women 8. Substance abuse (drug or alcohol) or any other factor (e.g., serious psychiatric condition) within the last 5 years that could limit the subject's ability to comply with study procedures 9. Subjects who are detained officially or legally to an official institute or those that have been committed to an institution by virtue of an order issued either by the judicial or the administrative authorities will be excluded from the study 10. Use of omalizumab within the last 3 months 11. Receipt of intravenous IgG therapy 30 days prior to Baseline 12. Plasmapheresis 30 days prior to Baseline 13. Use (daily or every other day) of Doxepin 14 days prior to Baseline 14. Receipt of inactive vaccination or live attenuated vaccine 30 days prior to Baseline 15. Use of H2 antihistamines 7 days before Baseline 16. Intake of leukotriene antagonists within 7 days prior to enrollment 17. Intake of systemic corticosteroids (e.g., oral or depot) within 14 days prior to enrollment 18. Positive screening for ova and parasite test at Baseline 19. Treatment of helminthic parasite within 6 months of screening 20. Positive HIV serology at screening 21. Positive Hepatitis serology at baseline, except for vaccinated patients or patients with past but resolved hepatitis at screening 22. Donation or loss of \>500ml of blood within 56 days prior to administration of study drug or donation of plasma within 7 days prior to administration of drug 23. Known hypersensitivity to any ingredients of AK002 or drugs related to AK002 (e.g., monoclonal antibodies, polyclonal gamma globulin)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Urticaria Control Test (UCT) Score From Baseline to Week 22 in the Main Study Phase | Baseline to Week 22 (Main Study Phase) | The UCT score consists of 4 items, and each UCT item has 5 answer options (scored with 0-4 points), where low points indicate high disease activity and low disease control of chronic urticaria. The UCT score, ranging from 0 to 16, is calculated by adding all 4 individual item scores. A UCT score of 16 points indicates complete disease control and a change of the UCT score of 3 or more points was regarded as clinically relevant (minimal clinically important difference \[MCID\]). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of up to 12 Additional Doses of AK002 in Subjects With CU in the Extended Dosing Phase | Through study completion, up to 52 weeks (Extension Dosing Phase) | Adverse events were assessed during the Extended Dosing Phase of the study, and only the 5 subjects who entered the Extended Dosing Phase were included. |
Countries
Germany, United States
Participant flow
Recruitment details
47 subjects were enrolled in the main study and received at least one dose of AK002. 45 subjects had at least one post-baseline assessment of the primary efficacy variable and were reported in the baseline period. 5 subjects from the main study were allowed the option to receive extended dosing with up to 12 additional doses of AK002.
Pre-assignment details
no pre-assignment was done
Participants by arm
| Arm | Count |
|---|---|
| AK002 For the main study, single doses of AK002 were administered by IV infusion every 28 days at Weeks 0, 4, 8, 12, 16, and 20. The arm included all subjects who were enrolled in the main study, did receive at least 1 dose of the study drug, and had at least 1 post-baseline assessment of the primary efficacy variable (=modified intention-to-treat population, mITT).
For the extended dosing phase, the arm included all subjects who were enrolled in the extended dosing and received at least 1 dose of the study drug. | 45 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Extended Dosing | Patient decision | 1 |
| Main Study | Adverse Event | 4 |
| Main Study | Death | 1 |
| Main Study | Lost to Follow-up | 1 |
| Main Study | Non-Specific | 2 |
| Main Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | AK002 |
|---|---|
| Age, Continuous Extended Dosing Phase | 43 years |
| Age, Continuous Main Study Phase | 42 years |
| Ethnicity (NIH/OMB) Extended Dosing Phase Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Extended Dosing Phase Not Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Extended Dosing Phase Unknown or Not Reported | 0 Participants |
| Ethnicity (NIH/OMB) Main Study Phase Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Main Study Phase Not Hispanic or Latino | 43 Participants |
| Ethnicity (NIH/OMB) Main Study Phase Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) Extended Dosing Phase American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Extended Dosing Phase Asian | 0 Participants |
| Race (NIH/OMB) Extended Dosing Phase Black or African American | 0 Participants |
| Race (NIH/OMB) Extended Dosing Phase More than one race | 0 Participants |
| Race (NIH/OMB) Extended Dosing Phase Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Extended Dosing Phase Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) Extended Dosing Phase White | 5 Participants |
| Race (NIH/OMB) Main Study Phase American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Main Study Phase Asian | 0 Participants |
| Race (NIH/OMB) Main Study Phase Black or African American | 1 Participants |
| Race (NIH/OMB) Main Study Phase More than one race | 0 Participants |
| Race (NIH/OMB) Main Study Phase Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Main Study Phase Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) Main Study Phase White | 44 Participants |
| Region of Enrollment Germany | 29 Participants |
| Region of Enrollment United States | 16 Participants |
| Sex: Female, Male Extended Dosing Phase Female | 5 Participants |
| Sex: Female, Male Extended Dosing Phase Male | 0 Participants |
| Sex: Female, Male Main Study Phase Female | 34 Participants |
| Sex: Female, Male Main Study Phase Male | 11 Participants |
| Urticaria Control Test (UCT) Score Extended Dosing Phase | 1.6 Score on a scale STANDARD_DEVIATION 1.5 |
| Urticaria Control Test (UCT) Score Main Study Phase | 4.4 Score on a scale STANDARD_DEVIATION 3.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 47 | 0 / 5 |
| other Total, other adverse events | 33 / 47 | 5 / 5 |
| serious Total, serious adverse events | 4 / 47 | 1 / 5 |
Outcome results
Primary
Change in Urticaria Control Test (UCT) Score From Baseline to Week 22 in the Main Study Phase
The UCT score consists of 4 items, and each UCT item has 5 answer options (scored with 0-4 points), where low points indicate high disease activity and low disease control of chronic urticaria. The UCT score, ranging from 0 to 16, is calculated by adding all 4 individual item scores. A UCT score of 16 points indicates complete disease control and a change of the UCT score of 3 or more points was regarded as clinically relevant (minimal clinically important difference \[MCID\]).
Time frame: Baseline to Week 22 (Main Study Phase)
Population: Modified intention-to-treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CholU | Change in Urticaria Control Test (UCT) Score From Baseline to Week 22 in the Main Study Phase | 6.5 Score on a scale | Standard Deviation 6.15 |
| UF-Cohort | Change in Urticaria Control Test (UCT) Score From Baseline to Week 22 in the Main Study Phase | 3.4 Score on a scale | Standard Deviation 4.09 |
| CSU-XN | Change in Urticaria Control Test (UCT) Score From Baseline to Week 22 in the Main Study Phase | 11.1 Score on a scale | Standard Deviation 4.07 |
| CSU-XF | Change in Urticaria Control Test (UCT) Score From Baseline to Week 22 in the Main Study Phase | 4.8 Score on a scale | Standard Deviation 6.97 |
Other Pre-specified
Safety and Tolerability of up to 12 Additional Doses of AK002 in Subjects With CU in the Extended Dosing Phase
Adverse events were assessed during the Extended Dosing Phase of the study, and only the 5 subjects who entered the Extended Dosing Phase were included.
Time frame: Through study completion, up to 52 weeks (Extension Dosing Phase)
Population: 5 subjects from the main study were enrolled in the Extended Dosing Phase.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CholU | Safety and Tolerability of up to 12 Additional Doses of AK002 in Subjects With CU in the Extended Dosing Phase | Subjects with ≥1 adverse events | 5 Participants |
| CholU | Safety and Tolerability of up to 12 Additional Doses of AK002 in Subjects With CU in the Extended Dosing Phase | Subjects with ≥1 treatment-related adverse events | 4 Participants |
| CholU | Safety and Tolerability of up to 12 Additional Doses of AK002 in Subjects With CU in the Extended Dosing Phase | Subjects with an adverse event leading to study drug discontinuation | 0 Participants |
| CholU | Safety and Tolerability of up to 12 Additional Doses of AK002 in Subjects With CU in the Extended Dosing Phase | Subjects with ≥1 serious adverse events | 1 Participants |
| CholU | Safety and Tolerability of up to 12 Additional Doses of AK002 in Subjects With CU in the Extended Dosing Phase | Subjects with ≥1 treatment-related serious adverse events | 0 Participants |